The C-terminal amidated analogue of the substance P (SP) fragment SP1-7 attenuates the expression of naloxone-precipitated withdrawal in morphine dependent rats

We previously demonstrated that intracerebroventricular (i.c.v.) administration of the substance P (SP) aminoterminal fragment SP1-7 attenuates the expression of morphine withdrawal in the male rat. In this study we have used a synthetic analogue of this peptide, i.e. the SP1-7 amide showing higher binding potency than the native heptapeptide, in a similar experimental set-up. Thus, Wistar male rats were made tolerant to morphine by daily injections of the opiate during 8 days. Following peptide administration (i.c.v.) and a subsequent naloxone challenge a variety of physical syndromes of withdrawal were recorded. We observed that the SP1-7 amide potently and dose-dependently reduced several signs of reaction to morphine withdrawal. Interestingly, the effect of the peptide amide was significantly attenuated by the addition of the sigma agonist (+)-SKF-10047. We conclude that the SP1-7 amide mimics the effect of the native SP fragment and that the mechanisms for its action involve a sigma receptor site. (C) 2009 Elsevier Inc. All rights reserved.